The addition of cellular imaging to high-speed, single-cell flow cytometry has revolutionized simultaneous immunophenotyping with morphological and spatial insights.
We have pioneered the utilization of imaging-enabled platforms such as the CytPix and FACSDiscover to characterize cell biology. The CytPix combines standard flow cytometry with a 20X equivalent brightfield camera to provide detailed morphological information, while the FACSDiscover enables cellular marker localization using three fluorescence imaging detectors in addition to a full spectral cytometer.
Both platforms process images at ultra-high throughput, with FACSDiscover reaching up to 10,000 cells per second. Imaging-derived features and AI-based analysis provide morphological and spatial information, uncovering insights not possible with traditional flow cytometry. This includes enhanced identification of immune cell subsets with unique functionalities, improved resolution of senescence, and more detailed signaling and metabolic characterization of mitochondrial activity and distribution. Moreover, imaging cytometry allows to characterize immunological synapses, which was previously impossible with flow cytometry.
Current developments include leveraging AI to identify cellular states and activation label-free, simplifying cellular characterization and profiling, and bridging phenotype with mechanism–thereby driving innovation in immune cell research across multiple therapeutic areas.
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Technological Innovations in Immunology (TECH)
Nicola Heller, Viji Premkumar, Nicholas G. Battaglia et al.· Journal of Immunology· 0 citations
mRNA-encoded virus-like particles (VLPs) are an emerging advancement in vaccine technology, enabling the self-assembly of viral antigens into structures that closely resemble native viruses. This innovative approach to conventional mRNA vaccination may boost vaccine-induced adaptive immune responses and allow for reduced dosing. To evaluate this technology, we developed AZD6563, an mRNA VLP vaccine targeting the COVID-19 XBB1.5 spike variant.
The phase 1 clinical study ARTEMIS-C was conducted to assess cellular immunogenicity in adults aged 18—64 years and ≥65 years following administration of AZD6563 (5 µg or 10 µg) or the licensed BNT162b2 XBB.1.5 mRNA vaccine (30 µg).
AZD6563 drove spike-specific CD4+ and CD8+ T cell responses comparable to those elicited by higher dose of BNT162b2. Functional analysis of these cells revealed similar cytokine production profiles across groups; however, the 10µg dose of AZD6563 led to higher TCR diversity within the ≥65-year cohort. Notably, expansion of spike-specific B cells was most pronounced in the AZD6563 10µg group, with marked increases in cross-reactive XBB.1.5 spike-specific B cells that also recognized Omicron BA.4/5 and ancestral SARS-CoV-2 variants.
Collectively, these results demonstrate that AZD6563, at reduced doses, matches the cellular immunogenicity of BNT162b2 while enhancing B cell cross-reactivity and TCR diversity in older adults, supporting its potential as a next-generation COVID-19 vaccine candidate.
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Vaccines and Immunotherapy (VAC)
Michael Powell, Nicholas G. Battaglia, Lee-Jah Chang et al.· Journal of Immunology· 0 citations